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Ulcerative colitis
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==Diagnosis== [[Image:Ulcerative colitis.jpg|thumb|[[Endoscopic]] image of ulcerative colitis affecting the left side of the colon. The image shows confluent superficial ulceration and loss of mucosal architecture. Crohn's disease may be similar in appearance, a fact that can make diagnosing UC a challenge.]] [[Image:Ulcerative colitis (2) active.jpg|thumb|H&E stain of a colonic biopsy showing a crypt abscess, a classic finding in ulcerative colitis]] The initial [[medical diagnosis|diagnostic]] workup for ulcerative colitis consists of a complete history and physical examination, assessment of signs and symptoms, laboratory tests and endoscopy.<ref name=Dassopoulos>{{cite journal | vauthors = Dassopoulos T, Cohen RD, Scherl EJ, Schwartz RM, Kosinski L, Regueiro MD | title = Ulcerative Colitis Care Pathway | journal = Gastroenterology | volume = 149 | issue = 1 | pages = 238β245 | date = July 2015 | pmid = 26025078 | doi = 10.1053/j.gastro.2015.05.036 }}</ref> Severe UC can exhibit high erythrocyte sedimentation rate (ESR), decreased albumin (a protein produced by the liver), and various changes in electrolytes. As discussed previously, UC patients often also display elevated alkaline phosphatase. Inflammation in the intestine may also cause higher levels of fecal calprotectin or lactoferrin.<ref name=":4">{{cite journal |last1=Nikolaus |first1=Susanna |last2=Schreiber |first2=Stefan |date=November 2007 |title=Diagnostics of inflammatory bowel disease |url=https://pubmed.ncbi.nlm.nih.gov/17983810/ |journal=Gastroenterology |volume=133 |issue=5 |pages=1670β1689 |doi=10.1053/j.gastro.2007.09.001 |issn=1528-0012 |pmid=17983810}}</ref> Specific testing may include the following:<ref name="ACG_Guidelines_2019" /><ref name="emed2336">{{eMedicine|med|2336|Ulcerative colitis}}</ref> * A [[complete blood count]] is done to check for anemia; [[thrombocytosis]], a high [[platelet]] count, is occasionally seen * [[Electrolyte]] studies and [[renal function|kidney function tests]] are done, as chronic diarrhea may be associated with [[hypokalemia]], [[hypomagnesemia]] and kidney injury. * [[Liver function tests]] are performed to screen for bile duct involvement: [[primary sclerosing cholangitis]]. * Imaging such as [[x-ray]] or CT scan to evaluate for possible perforation or [[toxic megacolon]] * [[Stool culture]] and ''[[Clostridioides difficile]]'' stool assay to rule out infectious colitis<ref name="Dassopoulos" /> * [[Inflammatory markers]], such as erythrocyte sedimentation rate or [[C-reactive protein]] * Lower endoscopy to evaluate the rectum and distal large intestine ([[sigmoidoscopy]]) or entire colon and end of the [[small intestine]] (colonoscopy) for ulcers and inflammation Although ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease.<ref name="ACG_Guidelines_2019" /> The [[simple clinical colitis activity index]] was created in 1998 and is used to assess the severity of symptoms.<ref name="WalmsleyAyres1998">{{cite journal | vauthors = Walmsley RS, Ayres RC, Pounder RE, Allan RN | title = A simple clinical colitis activity index | journal = Gut | volume = 43 | issue = 1 | pages = 29β32 | date = July 1998 | pmid = 9771402 | pmc = 1727189 | doi = 10.1136/gut.43.1.29 }}</ref><!-- please retain this historical, non-MEDRS citation --> ===Endoscopic=== [[Image:Chronic Ulcerative Colitis 1.jpg|thumb|Colonic [[pseudopolyps]] of a person with intractable UC, [[colectomy]] specimen]] The best test for diagnosis of ulcerative colitis remains [[endoscopy]], which is examination of the internal surface of the bowel using a flexible camera. Initially, a flexible sigmoidoscopy may be completed to establish the diagnosis.<ref name="Lamb" /> The physician may elect to limit the extent of the initial exam if severe colitis is encountered to minimize the risk of [[Bowel perforation|perforation]] of the colon. However, a complete colonoscopy with entry into the terminal ileum should be performed to rule out Crohn's disease, and assess extent and severity of disease.<ref name="Lamb">{{cite journal | vauthors = Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MC, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB | title = British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults | journal = Gut | volume = 68 | issue = Suppl 3 | pages = s1βs106 | date = December 2019 | pmid = 31562236 | pmc = 6872448 | doi = 10.1136/gutjnl-2019-318484 }}</ref> Endoscopic findings in ulcerative colitis include: [[erythema]] (redness of the [[mucosa]]), [[friability]] of the mucosa, superficial ulceration, and loss of the vascular appearance of the colon. When present, ulcerations may be confluent. Pseudopolyps may be observed.<ref>{{cite journal | vauthors = Politis DS, Papamichael K, Katsanos KH, Koulouridis I, Mavromati D, Tsianos EV, Christodoulou DK | title = Presence of pseudopolyps in ulcerative colitis is associated with a higher risk for treatment escalation | journal = Annals of Gastroenterology | volume = 32 | issue = 2 | pages = 168β173 | date = March 2019 | pmid = 30837789 | pmc = 6394261 | doi = 10.20524/aog.2019.0357 }}</ref> Ulcerative colitis is usually continuous from the rectum, with the rectum almost universally being involved. Perianal disease is rare. The degree of involvement endoscopically ranges from proctitis (rectal inflammation) to left sided colitis (extending to descending colon), to extensive colitis (extending proximal to descending colon).<ref name=":1" /> ===Histologic=== [[Image:Ulcerative colitis (2) endoscopic biopsy.jpg|thumb|left|Biopsy sample ([[H&E stain]]) that demonstrates marked [[lymphocyte|lymphocytic]] infiltration (blue/purple) of the [[intestinal mucosa]] and architectural distortion of the crypts.]] [[File:Histopathology of a crypt abscess.jpg|thumb|Crypt abscess. H&E stain.]] [[Biopsy|Biopsies]] of the mucosa are taken during endoscopy to confirm the diagnosis of UC and differentiate it from Crohn's disease, which is managed differently clinically. Histologic findings in ulcerative colitis includes: distortion of [[Intestinal crypt|crypt]] architecture, crypt abscesses, and inflammatory cells in the mucosa (lymphocytes, plasma cells, and granulocytes).<ref name="Feuerstein_UC" /> Unlike the transmural inflammation seen in Crohn's disease, the inflammation of ulcerative colitis is limited to the mucosa.<ref name="Feuerstein_UC" /> ===Laboratory tests=== Blood and stool tests serve primarily to assess disease severity, level of inflammation and rule out causes of infectious colitis. All individuals with suspected ulcerative colitis should have stool testing to rule out infection.<ref name="Ungaro" /> A [[complete blood count]] may demonstrate anemia, leukocytosis, or thrombocytosis.<ref name="Ungaro" /> Anemia may be caused by inflammation or bleeding. Chronic blood loss may lead to iron deficiency as a cause for anemia, particularly microcytic anemia (small red blood cells), which can be evaluated with a serum [[ferritin]], [[Serum iron|iron]], [[total iron-binding capacity]] and [[transferrin saturation]]. Anemia may be due to a complication of treatment from azathioprine, which can cause low blood counts,<ref>{{cite web |title=Azathioprine Product Information |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017391s015lbl.pdf |website=Access FDA |publisher=Food and Drug Administration}}</ref> or sulfasalazine, which can result in folate deficiency. Thiopurine metabolites (from azathioprine) and a folate level can help.<ref>{{cite journal | vauthors = Dignass AU, Gasche C, Bettenworth D, BirgegΓ₯rd G, Danese S, Gisbert JP, Gomollon F, Iqbal T, Katsanos K, Koutroubakis I, Magro F, Savoye G, Stein J, Vavricka S | title = European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases | journal = Journal of Crohn's & Colitis | volume = 9 | issue = 3 | pages = 211β222 | date = March 2015 | pmid = 25518052 | doi = 10.1093/ecco-jcc/jju009 | doi-access = free }}</ref> UC may cause high levels of inflammation throughout the body, which may be quantified with serum inflammatory markers, such as CRP and ESR. However, elevated inflammatory markers are not specific for UC and elevations are commonly seen in other conditions, including infection. In addition, inflammatory markers are not uniformly elevated in people with ulcerative colitis. Twenty five percent of individuals with confirmed inflammation on endoscopic evaluation have a normal CRP level.<ref name="ACG_Guidelines_2019">{{cite journal | vauthors = Rubin DT, Ananthakrishnan AN, Siegel CA, Sauer BG, Long MD | title = ACG Clinical Guideline: Ulcerative Colitis in Adults | journal = The American Journal of Gastroenterology | volume = 114 | issue = 3 | pages = 384β413 | date = March 2019 | pmid = 30840605 | doi = 10.14309/ajg.0000000000000152 | s2cid = 73473272 | doi-access = free }}</ref> [[Serum albumin]] may also be low related to inflammation, in addition to loss of protein in the GI tract associated with bleeding and colitis. [[Vitamin D deficiency|Low serum levels of vitamin D]] are associated with UC, although the significance of this finding is unclear.<ref>{{cite journal | vauthors = Del Pinto R, Pietropaoli D, Chandar AK, Ferri C, Cominelli F | title = Association Between Inflammatory Bowel Disease and Vitamin D Deficiency: A Systematic Review and Meta-analysis | journal = Inflammatory Bowel Diseases | volume = 21 | issue = 11 | pages = 2708β2717 | date = November 2015 | pmid = 26348447 | pmc = 4615394 | doi = 10.1097/MIB.0000000000000546 | doi-access = free }}</ref> Specific antibody markers may be elevated in ulcerative colitis. Specifically, [[perinuclear antineutrophil cytoplasmic antibodies]] (pANCA) are found in 70 percent of cases of UC.<ref name="ACG_Guidelines_2019" /> Antibodies against ''[[Saccharomyces cerevisiae]]'' may be present, but are more often positive in Crohn's disease compared with ulcerative colitis. However, due to poor accuracy of these serolologic tests, they are not helpful in the diagnostic evaluation of possible inflammatory bowel disease.<ref name="ACG_Guidelines_2019" /><ref name="Feuerstein_UC" /> Several stool tests may help quantify the extent of inflammation present in the colon and rectum. [[Fecal calprotectin]] is elevated in inflammatory conditions affecting the colon, and is useful in distinguishing irritable bowel syndrome (noninflammatory) from a flare in inflammatory bowel disease.<ref name="ACG_Guidelines_2019" /> Fecal calprotectin is 88% sensitive and 79% specific for the diagnosis of ulcerative colitis.<ref name="ACG_Guidelines_2019" /> If the fecal calprotectin is low, the likelihood of inflammatory bowel disease are less than 1 percent.<ref name="Ungaro" /> [[Lactoferrin]] is an additional nonspecific marker of intestinal inflammation.<ref>{{cite journal | vauthors = Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG | title = C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis | journal = The American Journal of Gastroenterology | volume = 110 | issue = 6 | pages = 802β19; quiz 820 | date = June 2015 | pmid = 25964225 | doi = 10.1038/ajg.2015.120 | s2cid = 26111716 }}</ref> === Imaging === Overall, imaging tests, such as [[x-ray]] or CT scan, may be helpful in assessing for complications of ulcerative colitis, such as perforation or toxic megacolon. Bowel ultrasound (US) is a cost-effective, well-tolerated, non-invasive and readily available tool for the management of patients with inflammatory bowel disease (IBD), including UC, in clinical practice.<ref>{{cite journal | vauthors = Bryant RV, Friedman AB, Wright EK, Taylor KM, Begun J, Maconi G, Maaser C, Novak KL, Kucharzik T, Atkinson NS, Asthana A, Gibson PR | title = Gastrointestinal ultrasound in inflammatory bowel disease: an underused resource with potential paradigm-changing application | journal = Gut | volume = 67 | issue = 5 | pages = 973β985 | date = May 2018 | pmid = 29437914 | doi = 10.1136/gutjnl-2017-315655 | s2cid = 3344377 }}</ref> Some studies demonstrated that bowel ultrasound is an accurate tool for assessing disease activity in people with ulcerative colitis.<ref>{{cite journal |last1=Allocca |first1=Mariangela |last2=Filippi |first2=Elisabetta |last3=Costantino |first3=Andrea |last4=Bonovas |first4=Stefanos |last5=Fiorino |first5=Gionata |last6=Furfaro |first6=Federica |last7=Peyrin-Biroulet |first7=Laurent |last8=Fraquelli |first8=Mirella |last9=Caprioli |first9=Flavio |last10=Danese |first10=Silvio |title=Milan ultrasound criteria are accurate in assessing disease activity in ulcerative colitis: external validation |journal=United European Gastroenterology Journal |date=May 2021 |volume=9 |issue=4 |pages=438β442 |doi=10.1177/2050640620980203 |pmid=33349199 |pmc=8259285 |doi-access=free }}</ref><ref>{{cite journal |last1=Allocca |first1=Mariangela |last2=Fiorino |first2=Gionata |last3=Bonovas |first3=Stefanos |last4=Furfaro |first4=Federica |last5=Gilardi |first5=Daniela |last6=Argollo |first6=Marjorie |last7=Magnoni |first7=Paola |last8=Peyrin-Biroulet |first8=Laurent |last9=Danese |first9=Silvio |title=Accuracy of Humanitas Ultrasound Criteria in Assessing Disease Activity and Severity in Ulcerative Colitis: A Prospective Study |journal=Journal of Crohn's and Colitis |date=28 November 2018 |volume=12 |issue=12 |pages=1385β1391 |doi=10.1093/ecco-jcc/jjy107 |pmid=30085066 |pmc=6260119 |doi-access=free }}</ref><ref>Piazza O Sed N, Noviello D, Filippi E, Conforti F, Furfaro F, Fraquelli M, Costantino A, Danese S, Vecchi M, Fiorino G, Allocca M, Caprioli F. Superior predictive value of transmural over endoscopic severity for colectomy risk in ulcerative colitis: a multicentre prospective cohort study. J Crohns Colitis. 2024 Feb 26;18(2):291-299. doi: 10.1093/ecco-jcc/jjad152. PMID: 37632350; PMCID: PMC10896635.</ref> Imaging is otherwise of limited use in diagnosing ulcerative colitis.<ref name="Ungaro" /><ref name="Feuerstein_UC" /> Magnetic resonance imaging (MRI) is necessary to diagnose underlying PSC.<ref name="Feuerstein_UC" /> Abdominal xray is often the test of choice and may display nonspecific findings in cases of mild or moderate ulcerative colitis. In circumstances of severe UC, radiographic findings may include thickening of the mucosa, often termed "thumbprinting", which indicates swelling due to fluid displacement (edema). Other findings may include colonic dilation and stool buildup evidencing constipation.<ref name=":4" /> Similar to xray, in mild ulcerative colitis, double contrast barium enema often shows nonspecific findings. Conversely, barium enema may display small buildups of barium in microulcerations. Severe UC can be characterized by various polyps, colonic shortening, loss of haustrae (the small bulging pouches in the colon), and narrowing of the colon. It is important to note that barium enema should not be conducted in patients exhibiting very severe symptoms as this may slow or stop stool passage through the colon causing ileus and toxic megacolon.<ref name=":4" /> Other methods of imaging include computed tomography (CT) and magnetic resonance imaging (MRI). Both may depict colonic wall thickening but have decreased ability to find early signs of wall changes when compared to barium enema. In cases of severe ulcerative colitis, however, they often exhibit equivalent ability to detect colonic changes.<ref name=":4" /> Doppler ultrasound is the last means of imaging that may be used. Similar to the imaging methods mentioned earlier, this may show some thickened bowel wall layers. In severe cases, this may show thickening in all bowel wall layers (transmural thickness).<ref name=":4" /> === Differential diagnosis === Several conditions may present in a similar manner as ulcerative colitis and should be excluded. Such conditions include: Crohn's disease, infectious colitis, [[nonsteroidal anti-inflammatory drug]] enteropathy, and [[irritable bowel syndrome]]. Alternative causes of colitis should be considered, such as [[ischemic colitis]] (inadequate blood flow to the colon), [[radiation colitis]] (if prior exposure to [[radiation therapy]]), or [[chemical colitis]]. [[Pseudomembranous colitis]] may occur due to [[Clostridioides difficile infection|''Clostridioides difficile'' infection]] following administration of antibiotics. ''[[Entamoeba histolytica]]'' is a protozoan parasite that causes intestinal inflammation. A few cases have been misdiagnosed as UC with poor outcomes occurring due to the use of corticosteroids.<ref>{{cite journal | vauthors = Shirley DA, Moonah S | title = Fulminant Amebic Colitis after Corticosteroid Therapy: A Systematic Review | journal = PLOS Neglected Tropical Diseases | volume = 10 | issue = 7 | pages = e0004879 | date = July 2016 | pmid = 27467600 | pmc = 4965027 | doi = 10.1371/journal.pntd.0004879 | doi-access = free }}</ref> The most common disease that mimics the symptoms of ulcerative colitis is Crohn's disease, as both are inflammatory bowel diseases that can affect the colon with similar symptoms. It is important to differentiate these diseases since their courses and treatments may differ. In some cases, however, it may not be possible to tell the difference, in which case the disease is classified as indeterminate colitis.<ref>{{cite journal | vauthors = Tremaine WJ | title = Is indeterminate colitis determinable? | journal = Current Gastroenterology Reports | volume = 14 | issue = 2 | pages = 162β165 | date = April 2012 | pmid = 22314810 | doi = 10.1007/s11894-012-0244-x | s2cid = 40346031 }}</ref> Crohn's disease can be distinguished from ulcerative colitis in several ways. Characteristics that indicate Crohn's include evidence of disease around the anus (perianal disease). This includes anal fissures and abscesses as well as fistulas, which are abnormal connections between various bodily structures.<ref>{{cite journal |last1=Kim |first1=B. |last2=Barnett |first2=J. L. |last3=Kleer |first3=C. G. |last4=Appelman |first4=H. D. |date=November 1999 |title=Endoscopic and histological patchiness in treated ulcerative colitis |url=https://pubmed.ncbi.nlm.nih.gov/10566726/ |journal=The American Journal of Gastroenterology |volume=94 |issue=11 |pages=3258β3262 |doi=10.1111/j.1572-0241.1999.01533.x |issn=0002-9270 |pmid=10566726|hdl=2027.42/74642 |s2cid=11446833 |hdl-access=free }}</ref> Infectious colitis is another condition that may present in similar manner to ulcerative colitis. Endoscopic findings are also oftentimes similar. One can discern whether a patient has infectious colitis by employing tissue cultures and stool studies. Biopsy of the colon is another beneficial test but is more invasive. Other forms of colitis that may present similarly include radiation and diversion colitis. Radiation colitis occurs after irradiation and often affects the rectum or sigmoid colon, similar to ulcerative colitis. Upon histology radiation colitis may indicate eosinophilic infiltrates, abnormal epithelial cells, or fibrosis. Diversion colitis, on the other hand, occurs after portions of bowel loops have been removed. Histology in this condition often shows increased growth of lymphoid tissue. In patients who have undergone transplantation, graft versus host disease may also be a differential diagnosis. This response to transplantation often causes prolonged diarrhea if the colon is affected. Typical symptoms also include rash. Involvement of the upper gastrointestinal tract may lead to difficulty swallowing or ulceration. Upon histology, graft versus host disease may present with crypt cell necrosis and breakdown products within the crypts themselves.<ref>{{cite journal |last1=Woodruff |first1=J. M. |last2=Hansen |first2=J. A. |last3=Good |first3=R. A. |last4=Santos |first4=G. W. |last5=Slavin |first5=R. E. |date=December 1976 |title=The pathology of the graft-versus-host reaction (GVHR) in adults receiving bone marrow transplants |url=https://pubmed.ncbi.nlm.nih.gov/11596/ |journal=Transplantation Proceedings |volume=8 |issue=4 |pages=675β684 |issn=0041-1345 |pmid=11596}}</ref> {{Findings in CD vs. UC}}
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